This application requests funds to establish a multidisciplinary postdoctoral training program in mechanisms of cardiovascular disease focussed on drawing surgical trainees into basic laboratory investigation. e rationale for the program is to enhance and insure the development of basic and clinical investigators who have broadly based knowledge in the major fields related to research in cardiovascular disease. The in-depth background and experience obtained during the training period is intended to allow fellows to embark on careers as independent investigators. There is a clear need for investigators with a surgical viewpoint to undertake such training, as operative procedures and care of the surgical patient are closely tied to advances in research. The participating faculty is drawn from the Departments of Surgery, Physiology, Medicine and Pediatrics. The training plan will include research work in the laboratory of a faculty unit leader, selected graduate courses, a tutorial in the research area, research seminar presentations, and periodic evaluations by an Advisory Committee. The program includes eight laboratories or units, many of which have long-standing collaborative interactions. Dr. Stern is studying endothelial adaptive responses to hypoxemia, a novel cytokine produced by macrophages and tumor cells which modulates vascular properties, and the role of Factor IX/IXa in activation of coagulation induced by cardiopulmonary bypass. Dr. Spotnitz is studying ventricular function following cardiac preservation with the goal of relating parameters of ventricular mechanics to vascular dysfunction which accompanies prolonged cardiac preservation and rejection of allografts. Dr. Hardy is studying the role of vascular activation in the setting of allogeneic transplantation. Dr. Pinsky is studying vascular dysfunction following prolonged preservation of the heart and lung for transplantation, and has focussed on underlying molecular mechanisms at the level of cyclic nucleotide second messenger systems and expression of leukocyte adhesion molecules. Dr. Rose is studying the nature and vascular reactivity of cells which populate textured interior surfaces of left ventricular assist devices. Dr. Schmidt is examining vascular perturbation by advanced glycation endproducts, which are believed to contribute to diabetic vasculopathy in part through their interaction with a novel receptor expressed on endothelium. Dr. Tall is studying the structure and function of cholesterol ester transfer protein, a central mediator of HDL metabolism and reverse cholesterol transport. Dr. Tabas is studying cholesterol metabolism in foam cell development. These projects and unit leaders are brought together by a common focus on cells in the normal vessel wall, cellular elements which infiltrate in pathologic. situations, such as atherosclerosis, as well as the myocardium. Research projects in which trainees will participate concern dissection of the roles of these cells in maintenance of vascular homeostasis and their participation in pathologic events underlying the formation and progression of vascular lesions. Our goal is to draw on the talents and enthusiasm of surgical trainees in order to direct their attention to productive and long-term investigative careers.